Genetic, carcinogenic and teratogenic effects of radiofrequency fields1

Mutation Research 410 Ž1998. 141–165

Mini review

Genetic, carcinogenic and teratogenic effects of radiofrequency fields 1 L. Verschaeve ) , A. Maes VITO, EnÕironmental Toxicology Unit, Boeretang 200, B-2400 Mol, Belgium Received 9 November 1996; accepted 15 August 1997

Abstract This paper reviews the literature data on the genetic toxicology of radiofrequency ŽRF. radiation. Whereas in the past most studies were devoted to microwave ovens and radar equipment, it is now mobile telecommunication that attracts most attention. Therefore we focus on mobile telephone frequencies where possible. According to a great majority of the papers, radiofrequency fields, and mobile telephone frequencies in particular, are not genotoxic: they do not induce genetic effects in vitro and in vivo, at least under non-thermal exposure conditions, and do not seem to be teratogenic or to induce cancer. Yet, some investigations gave rather alarming results that should be confirmed and completed by further experiments. Among them the investigation of synergistic effects and of possible mechanisms of action should be emphasised. q 1998 Elsevier Science B.V. Keywords: Radiofrequency radiation; Carcinogenicity; Teratogenicity; Genetic toxicology

1. Introduction Radiofrequency fields, and especially microwaves Ž300 MHz–300 GHz. are a very important part of the electromagnetic spectrum with respect to their applications and possible health consequences. These non ionising radiations have relatively short wavelengths and high frequencies compared to, e.g., extreme low frequency fields, and therefore also a greater amount of energy which is sufficient to cause heating in conductive materials ŽFig. 1.. Close to the transmitter, these high-frequency fields may thus be ) Corresponding author. Tel.: q32 14 335217; Fax: q32 14 320372; E-mail: [email protected] 1 This is the second in a series of four papers, the first of which was published in Mutation Res. 387 Ž1997. pp. 165–171.

harmful to human beings by producing thermal effects that may sometimes, when thermoregulation processes are insufficient, produce irreversible damage Že.g. cataract; w1,2x.. This kind of effect is well known from animal experiments and for that reason does not constitute a particular health problem, as measures can be taken to prevent excessive exposure. But also low-level exposures leading to nonthermal effects are, at least according to certain investigators, possible. Non-thermal effects have been reported in cell cultures and animals, in response to exposure to low-level fields. They are not well established and therefore highly controversial. While in the past decade people were especially concerned about the safety of microwave ovens Ž2450 MHz. and even before radar equipment, it is wireless communications Že.g. mobile telephones. that is par-

1383-5742r98r$19.00 q 1998 Elsevier Science B.V. All rights reserved. PII S 1 3 8 3 - 5 7 4 2 Ž 9 7 . 0 0 0 3 7 - 9

142

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

Fig. 1. The electromagnetic spectrum.

ticularly considered at present. It is now indeed generally accepted that modern microwave ovens are harmless Žleakage of microwaves from ovens is insignificant. at least when properly used, whereas a number of investigations on radar operators has identified some ‘‘thermal’’ effects that lead to safety precautions minimising the hazards. But little is known about the health hazards of cellular telephones that are rapidly gaining popularity. There are several systems in use which allow many users to communicate via the system simultaneously. The dominant access technique in Europe is the so-called TDMA technique ŽTime Division Multiple Access. which is used in GSM ŽGlobal System for Mobile communication., DECT ŽDigital European Cordless Telecommunications., DCS 1800 ŽDigital personal Communication System. and in TETRA ŽTrans European Trunked RAdio. systems. The carrier frequency bands allocated for these services are set mainly in the spectrum regions of 800–900 MHz and 1.8–2.2 GHz. With regard to these Žand other mobile phone. systems, one has to distinguish the possible effects emanating from transmission antennas and mobile base station antennas from the mobile phone handset itself. People may be exposed to all these

sources, but it is the handset that is most often suspected of having deleterious effects. There is a concern that, as the antenna of the handset is brought close to the head when calls are made or received, there may be a thermal insult at the molecular or cellular level. According to some scientists part of the microwave-energy is absorbed by the head and may eventually produce so-called ‘hot-spots’ in the brain Že.g. w3,4x.. Also, non-thermal effects are often anticipated. Most often headache, eye injury and cancer are mentioned as potential biological effects w5x. However, the only established possible dangerous effect of mobile phones is the interference in some circumstances with pacemakers and other apparatus prompting a warning to users from health authorities Že.g. w6x.. With regard to headache, cancer or other serious illnesses, little is known for sure. Therefore there is an urgent need for the updating of our knowledge. Indeed, not only the general public, but also some of the scientists involved in research on microwave or radiofrequency bioeffects are sufficiently worried about the possible adverse health effects of present-day mobile telephones to recommend restricted use of mobile phone handsets. A few even advise not to use them at all. Although most

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

scientists claim that no research to date suggests serious cause for concern, they all agree that the explosive growth in use of mobile telephones ŽIn 1995 there were over 85 million mobile telephone subscribers world-wide. justifies further research. In this paper we review the investigations that have been performed on the genotoxic effects of radiofrequency fields, including investigations on cancer and teratogenic effects.

2. Quantities and units Non ionising radiations are those electromagnetic radiations with a wavelength equal or higher than 10y7 m. The different non-ionising radiations are given in Fig. 1 where it can be seen that wavelength, frequency and photon energy are inter-related. Nonionising radiations have photon energies lower than approximately 12 eV, which is considered the boundary with ionising radiations. This energy is too low to induce ionisations of molecules and too low to break even the weakest chemical bond. Quantities and units differ greatly between the different kinds of electromagnetic radiations as the physical, but also the biological properties differ greatly. Therefore there is no such thing as an absorbed dose or dose-equivalent that we know from ionising radiations and that is common to all non-ionising electromagnetic fields or waves. High-frequency electromagnetic fields are quantified in terms of electric field strength E, expressed as volts per meter ŽVrm., and magnetic field strengths H, expressed as amperes per meter ŽArm.. A ‘dose’ to which the body or tissue or cells are exposed is expressed as the specific absorption ratio ŽSAR.. It gives an evaluation of the energy transfer to the body, tissue or cells per unit of time and per mass. It is expressed as watts per kilogram ŽWrkg.. In biological materials only the electric field contributes to energy absorption. The specific absorption rate is given by the following formula: SAR s < E < 2 srr where s is the electrical conductivity of the medium

143

Žin Siemens per meter. and r the density of the medium Žin kgrm3 .. The SAR can thus be calculated by above equation or measured Žby measurements of temperature increases in the exposed subject or object.. However, the ‘dosimetry’ remains a very complicated task, among others because of the different electrical properties of different tissues w4,7x. The SAR is, e.g., dependent on the radiation source, the exposed body Žor object. and its configuration. It should be noted that, whereas biological media do not have absorption mechanisms with regard to magnetic fields, rapidly varying magnetic fields might yet induce absorption through secondary induced electric currents. Exposure to fields can be in the near field, which is the region close to the source antenna, or in the far field. In the far field the high-frequency electromagnetic field is often quantified in terms of power flux density, expressed in units of watts per squared meter ŽWrm2 ..

3. Epidemiological investigations Epidemiological studies, unlike most laboratory studies, tend to take several years and can only give information on exposures that have already occurred in people. Therefore, as mobile telephone bio-effects are only a very recent concern, there are until now no published epidemiological investigations on cause-specific morbidity or mortality in relation to mobile telephone use. Up to now only limited preliminary notes were published on, e.g., the methodology of epidemiological research with respect to the use of wireless communication w8–10x. However, some epidemiological investigations were conducted in the past with regard to other radiofrequency fields and applications. These studies were, among others, related to occupational exposures to radar, populations living near military installations and near broadcasting towers, amateur radio operators and users of hand-held traffic radar devices Žfor review, see w5,10,11x.. Most studies were rather small and criticised, e.g. on grounds of wrong or insufficient data collection, the absence of any, or adequate dosimetry and the omission to investigate potential

144

Table 1 Overview of investigations on in vitro RF-induced genetic effects Exposure conditions

Biological endpoint

Results

Comments

Reference

Commercialised calf thymus DNA

Analysis of thermal denaturation curves

No difference with unexposed DNA

w59x

2.45 GHz, 15.2 Wrkg

Rat kangaroo cells

Chromosomal aberrations

Increased incidence of unstable chromosome aberrations

2 .4 5 G H z, mWrcm2

Chinese hamster cell lines

Cytological effects

2.45 GHz, 15 Wrkg, long-term exposure Žduring 320 days.

Rat kangaroo cells

Chromosome aberrations

C y to lo g ic a l e ffe c ts Žnuclear vacuoles, pycnic and decondensed chromosomes, chromosome breakage. Increased chromosome aberration frequency

Control and exposed DNA solutions were maintained at the same temperature The observed aberrations are more commonly associated with ionising radiations Effects observed under elevated temperature conditions

2.45 GHz, CW, 20 min exposure, SAR from 104 up to 200 Wrkg Žmild hyperthermia. 7.7 GHz, 2 W max. power output, SAR not reported

Human lymphocytes

Chromosomal aberrations and sister chromatid exchanges

No evidence of cytogenetic damage, even under mild hyperthemia

V79 Chinese cells

hamster

Cytogenetic effects

7.7 GHz, 2 W max. power output, SAR not reported

V79 Chinese cells

hamster

Cytogenetic effects

7.7 GHz, 2 W max. power output, SAR not reported 2.45 GHz, 50 Hz modulated, 30 and 120 min exposure, 75 Wrkg

Human lymphocytes

Cytogenetic effects

Human lymphocytes

Chromosome aberrations, micronuclei and sister chromatid exchanges

Increased w 3 Hxthymidine incorporation and chromosome aberrations Effect on colony forming ability, chrom osom e aberrations and micronuclei Chromosome aberrations and micronuclei Increased frequency of chromosome aberrations and micronuclei. No microwave induced sister chromatid exchange frequency or influence on the cell proliferation

RF-effects alone 2.45 GHz, CW, mWrcm2

94

0 – 200

w60x

w21x

A change in cell population by repeated passage of the cells and senescence may have influenced the results w62,63x

w61x

Thermal effect probable

w64x

Thermal effect probable

w23x

Thermal effect probable

w65x

Temperature computercontrolled at 36.18C during the complete exposure time. Yet a heating effect cannot be ruled out

w22x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

Biological model

Tradescantia

Micronuclei

Increased micronucleus frequency

96 GHz, 50 Hz amplitude modulated, 10 min exposure, 100 Wrkg 0.954 GHz from a GSM base-station, continuous, 60–120 min exposure

Human lymphocytes

Micronuclei

Increased micronucleus frequency

Human lymphocytes

Chromosome aberrations

Slight increase in chromosome aberration frequency after exposure

TEM or GTEM-cells; 440, 900 and 1800 MHz, exposure at 378C during 39 to 70 h

Human lymphocytes

No indications of any RF-induced cytogenetic damage

415 MHz, 10–30 min, 15 W

Human lymphocytes

Chromosome aberrations, sister chromatid exchanges, micronuclei, cell proliferation, HGPRTmutations Micronuclei

935.2 MHz, CW, 2 h exposure, SAR s 0.4 Wrkg

Human lymphocytes

Chromosome aberrations and DNA single strand breaks Žsingle cell gel electrophoresis assay.

CHO cells

SCEs

Human diploid fibroblasts

DNA repair

L5178Y mouse leukaemia cells

Forward mutation assay Žthymidine kinase locus.

Synergisms 2450 MHz pulsed, 49 mWrcm2 , SAR s 34 Wrkg. Cells are simultaneously irradiated and MMC exposed 350 and 850 MHz and 1.2 GHz, pulsed 1 to 10 mWrcm2 , SAR s 0.39– 4.5 Wrkg. RF irradiation of the cells followed UV irradiation 2450 MHz, pulsed, 48.8 mWrcm 2 SAR s 30 Wrkg. Cells are simultaneously irradiated and MMC exposed

Increased micro nucleus frequency

The effect occurred at field levels of 27.5 Vrm and 0.073 Arm which should not cause any significant heating of the samples Thermal increase of 58C

w24x

No increased DNA damage according to the alkaline comet assay Žunpublished results.

w66x

w20x

w67x

Increase in micronucleus frequency was related to the exposure time

No indication of direct DNA or chromosome effect

No increased SCE frequency in cells exposed to RFs alone or with MMC compared to MMC alone RF alone, either continuous or pulsed, has no effect on the DNA repair. RF exposure after UV damage also had no effect RF exposure alone is not mutagenic. RF does not affect either the inhibition of cell growth or the extent of mutagenesis resulting from treatment with MMC alone

w68x

w27x

w69x

w70x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

In situ exposure near various broadcasting antenna Ž 10 – 21 M H z short waves.

w71x

145

146

Table 1 Žcontinued. Biological model

Biological endpoint

2450 MHz, pulsed 49 mWrcm 2 , SAR s 33.8 Wrkg. Cells are simultaneously irradiated and adriamycin exposed

CHO cells

Cell cycle and SCEs

2450 M H z, pulsed 49 mWrcm 2 , SAR s 33.8 Wrkg. Cells are simultaneously irradiated and exposed to MMC and adriamycin

CHO cells

Chromosome aberrations

2450 MH 2 , pulsed, SAR ;40 Wrkg. Cells are simultaneously exposed to Proflavin

L5178Y mouse leukaemic cells

Forward mutations at the TK-locus

954 MHz, continuous, 15 W, 49 Vrm, SAR s1.56 Wrkg. Cells exposed to mitomycin C following RF-irradiation Žduring lymphocyte cultivation.

Human lymphocytes

SCE

935.2 MHz, CW, 2 h exposure, SAR s 0.4 Wrkg. Cells exposed to mitomycin C following RF-irradiation Žduring lymphocyte cultivation.

Human lymphocytes

SCE

progression

Results

Comments RF does not affect changes in cell progression caused by adriamycin. RF does not change the number of SCEs that were induced by adriamycin RF alone does not enhance the chromosome aberration frequency. No alteration in the extent of chromosome aberrations for the combined treatment compared to the chemicals alone RF alone is not mutagenic. No increased mutation frequency for the combined treatment compared to proflavin alone. No difference in colony size distribution of the mutant colonies RF alone did not increase the SCE frequency. The SCE frequency for the combined treatment was always higher than for MMC alone. There was no change in cell proliferation compared to control cultures The combined exposure ŽRFqMMC. revealed a weak effect compared to cells exposed to MMC alone

Reference w72x

w73x

w74x

w26x

w27x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

Exposure conditions

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

confounders. This is for example illustrated in a recent review paper w5x where five studies relevant to adult cancer and RF-exposure were extensively discussed. In a study on RF-exposed US Embassy personnel in Moscow no deleterious effects were found, but the limited number of cancer cases makes this study rather non-informative in comparison with other studies w12x. Milham w13x found an increased standard mortality ratio ŽSMR. for certain cancer sites in radio amateurs, but there was no adjustment for confounders and most subjects were also professionally exposed to Žother. electric and magnetic fields. Armstrong et al. w14x investigated electric utility workers in France and Quebec ŽCanada. who were exposed to different non-ionising radiation frequencies, including radiofrequencies. They especially found a relationship with lung cancer in one of the utilities ŽQuebec. whereas a less indicative relationship was found with stomach cancer in another utility ŽFrance.. These differences from one utility to another detract somewhat from the credibility of these findings regarding the connection between electromagnetic fields and cancer. An association between lung or respiratory system cancer and RFexposure was also found by Robinette et al. w15x, but these authors did not adjust for the possible influence of smoking. Finally, Szmigielski w16x examined the cancer morbidity in Polish career military personnel. He found an excess occurrence of cancers at several cancer sites but no individual assessment was made of exposure levels or duration and, apart from age, adjustments for other factors, e.g. possible carcinogen exposures, were not made. These, and other epidemiological investigations concerned many different modes of exposure and different frequencies. For several studies, the link between the subject’s occupation and actual exposure was questionable and very often exposure was also to extreme lowfrequency fields and different chemicals. Therefore, taking the limited epidemiological evidence together it must presently be concluded that no definite conclusion can be drawn so far, either about the mobile telephone Žno adequate data so far., or about other radiofrequency fields. A number of investigations are now being conducted with regard to cancer and other disorders, especially in the USA and Scandinavian countries, but the results of most of these studies are several years away.

147

4. Genetic toxicology: in vitro laboratory investigations Possible effects on DNA or chromosome structure in somatic cells are considered to be very important as these changes could be associated with cell death or, possibly, with the development of cancer. Furthermore, such effects in male or female germ cells are important, as surviving mutations might be passed on to the next generation. Many investigations of RF-induced genetic effects in somatic- as well as in germ cells, therefore, have already been conducted in many different cell and animal systems. Again, different frequencies were investigated with emphasis on the 2450 MHz frequency of microwave ovens. A number of frequencies used in mobile telecommunication were recently also investigated, but most of these studies are still going on. In the 1970s and 1980s, several investigations were performed on RF-induced genetic changes in microbial test systems, essentially including Escherichia coli, Salmonella typhimurium and Saccharomyces cereÕisiae. They gave invariably negative results and will therefore not be further discussed Žfor a review, see e.g. w17–19x.. In vitro investigations using different eukaryotic cell systems are described in Table 1. It can be seen that both positive and negative results were obtained. Most often, when some evidence for a genetic effect was reported, this could be ascribed to hyperthermia, as the exposure conditions were clearly or most probably thermal in nature. This was, for example, clearly the case in an investigation by d’Ambrosio et al. w20x who found an increased incidence of micronuclei in microwave exposed human lymphocytes. However, the exposure was accompanied by a thermal increase of 58C. Cytological effects were also found in Chinese hamster cells that were exposed to 2.45 GHz fields, but again these effects were observed under elevated temperature conditions w21x. Investigating the same microwave frequency, we exposed human whole blood cells in such a way that the temperature of the blood remained constant at 36.18C. The SAR was calculated as 75.5 Wrkg, which again clearly suggests that the observed chromosomal abnormalities in the lymphocytes were obtained under thermal exposure conditions w22x. In some instances a thermal effect might be anticipated

148

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

even if the exposure was described as ‘‘being comparable to everyday environmental conditions’’. SAR values or temperature measurements were missing but the data were so much resembling, e.g. thermal killing curves, that a thermal effect is more than probable Že.g. w23x.. Some non-thermal positive responses were also reported Že.g. w24x., but they could possibly be due to so called sporadic positive responses. Reviews of assays used to detect DNA alterations have shown that such sporadic positive responses are indeed obtained from time to time w25x. Yet, a number of positive results remain puzzling and should be further investigated. Because of the many negative findings Žespecially in bacteria and algae but also in mammalian or human cells. and as positive findings were almost invariably connected with thermal exposure conditions or with RF-independent situations, it may be concluded that in vitro RF-exposure appears not to induce any genetic damage under non-thermal conditions. Therefore we believe that synergistic investigations deserves special attention. Indeed, people are exposed to many different influences, and theoretically it may well be that a RF-exposure alone is ineffective whereas this exposure might enhance the mutagenicity, carcinogenicity or teratogenicity of chemical or physical factors. As shown in Table 1, most often no synergistic effect was found between the applied field and a number of known mutagens Že.g. mitomycin C, adriamycin, proflavin. when the exposures were simultaneous. However, when the RF-exposure precedes the mutagen, a synergistic effect is sometimes found. This was the case with mitomycin C in a recent investigation of 954-MHz waves emitted by the antenna of a GSM base station Ž15 W power output, SAR s 1.5 Wrkg. w26x. However, when cells were exposed waves to 935.2 MHz Ž4.5 W. followed by mitomycin C, synergism was much less evident w27x. We are presently investigating the possible synergistic effects of 450 MHz Ž15 W., and 900 MHz Ž2–50 W. fields with mitomycin C and X-rays, but so far the results are not very clear and predominantly negative. According to another investigation microwave radiation also increases the mutagenic properties of ethyl methanesulfonate ŽEMS. in CHO cells w28x. The above investigations reporting a synergistic action of RF-fields with chemical or physical agents corroborates the earlier

finding that microwaves enhance, in human cancers, the effects of some cytotoxic agents w29x. It should be stressed that, so far, no mechanistic studies have been conducted in order to explain the reported synergisms. As long as this is not done, the results are only of limited value.

5. Genetic toxicology: in vivo laboratory investigations Several studies were conducted over the past 20 years using Drosophila melanogaster as the test organism. As for the experiments with microorganisms, they all yielded negative results. Therefore we will also refer to the earlier mentioned review papers. As seen in Tables 2 and 3, experiments in mammals gave more conflicting results. This was true as well for investigations on germ cells as for investigations on somatic cells. 5.1. Testicular function and male infertility Most of the studies on reproduction and development of small mammals exposed to radiofrequencyand microwave radiation have shown effects that can be related to an increase in temperature. Several studies have shown, for example, that acute microwave exposure can affect spermatogenic epithelium and thus male fertility through a raising of the testicular temperature Že.g. w30,31x.. The primary spermatocytes were often identified as a particularly sensitive stage and the response identified as identical to conventional heating. Some of the investigations were conducted in anaesthetised rats and mice Že.g. w30–32x. and are therefore of little value with respect to the determination of acceptable limits of human exposure. Anaesthetised animals indeed show an altered temperature regulation. The exposure of conscious animals is thus of greater relevance to exposure standards. Here, experiments have shown that acute and chronic exposure of conscious mice and rats very often do not alter the testicular function or fertility Že.g. w33x.. Effects were only found in extreme conditions Že.g. extreme high increase in rectal andror testicular temperature.

Table 2 Overview of investigations on in vivo RF-induced genetic effects in somatic cells Animal species

Biological endpoint

Main results

Comments

References

2.45 GHz, SAR up to 21 Wrkg

Chinese hamsters

Chromosomal aberrations in blood lymphocytes

No RF-effect found

Rectal temperature increase of 1.68C in the high exposure group. Long cell cultivation time following exposure may disadvantage cells with cytogenetic damage

w75x

9.4 GHz, pulse-modulated, 1–100 Wrm2 , 1 hrday over 2 weeks

Male Balbrc mice

Chromosome aberrations in male germ cells exposed as spermatocytes

w76x

2.4 GHz, SAR s 21 Wrkg, chronic exposure 8 hrday for 28 days 2.45 GHz, CW, 2 hrday, 12, 150 and 200 days, 0.1 W r m 2 , SA R s 1.2 Wrkg 2.45 GHz, pulsed, 2 ms puls width, 500 pps, or CW, SAR s1.2 Wrkg, 2 h exposure 2.45 GHz Ž2 ms pulses, 500 pps., 2 h exposure at 2 mWrcm2 , SAR s1.2 Wrkg Naltrexone injections Ž1 mgrkg. before and after RF-exposure 2.45 GHz; 20 hrday, 7 daysrweek during 18 m onths; SA R s 1.0 Wrkg

Mouse

Sister chromatid exchanges in bone marrow cells DNA analysis with synthetic oligo probes

SAR dependent increase in the frequency of chromosome exchanges and other cytogenetic effects No RF-effect found

Altered band patterns of brain and testes DNA from exposed mice

w38x

Male Swiss albino mice

w77x

Male rats

Sprague-Dawley

DNA damage in brain cells by the single cell gel electrophoresis assay

Increased DNA damage for both continuous and pulsed fields

w39,40x

Male rats

Sprague-Dawley

DNA double-strand breaks in brain cells with the single cell gel electrophoresis assay

Increased DNA doublestrand breaks following RF-exposure. The effect was partially blocked by treatment with naltrexone

w41x

C3HrHeJ mice; prone to mammary tumours

Micronuclei in peripheral blood and bone marrow

No significant difference in exposed and sham-exposed animals

Also no difference in micronuclei between both groups when the animals with mammary tumours were considered separately

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

Exposure conditions

w125x

149

150

Table 3 Overview of investigations on in vivo RF-induced genetic effects with regard to reproduction and teratogenesis Animal species

Biological endpoint

Main results

Acute microwave exposure of testes

Anaesthetised rats and mice

Effects on male reproductive system

9.4 GHz, pulse-modulated, 1–100 Wrm2 , 1 hrd over 2 weeks

Mice

Effects on male reproductive system

Elevated testicular temperature and depletion of the spermatogonic epithelium Chromosome aberrations in male germ cells exposed as spermatocytes

2.45 GHz, 30 min exposure, half-body SAR s 30 Wrkg

Anaesthetised Mice

Effects on male reproductive system

2.45 GHz, Wrkg

Anaesthetised Mice

Effects on male reproductive system

1.3 GHz, pulse modulated Ž1 ms pulses at 600 pps., whole body SAR s 6.3 Wrkg; exposure 6 hrd for 9 days

Rats

Effects on male reproductive system

1.3 GHz, CW, exposure 8 h at SAR s9 Wrkg 2.45 GHz, SAR s 5.6 Wrkg, exposure for 80 h over a 4 w period

Conscious rats

Effects on male reproductive system Effects on male reproductive system

2.45 GHz, 100 mWrcm2 for 10 min; 50 mWrcm2 Ž3= over 1 day. or 4= over 2 weeks

Mice

Dominant lethality

No dominant lethality, increase in mutagenicity in some instances

2.45 GHz, CW, kWrm2 for 70 s

1.7

Mice

Dominant lethality

1.7 GHz, 50 Wrkg during 30 min

Mice

Dominant lethality

Increased dominant lethality, abnormal sperm morphology and reduced male fertility Induction of dominant lethals

SAR s 44

Conscious rats

Temperature dependent depletion of primary spermatocytes. Threshold at 398C Decreased sperm count and increase in abnormal sperm No statistical significant effect on daily sperm production, number of epididymal sperm, sperm morphology and mass of testes and epididymes No significant differences in testicular function Transient reduction in fertility

Comments

Reference w30x

SAR-dependent increase in the frequency of chromosome exchanges and other cytogenetic effects Response identical to that of conventional heating

w76x

Maximal effect at spermatocyte and spermatid exposure Body temperature raised by 1.58C

w31x

Rectal temperature raised by 4.58C Rectal temperature estimated to have raised to 418C and testicular temperature to 378C Žprobably no loss in fertility at lower temperatures. Males mated 6–7 weeks after exposure. Effects on mutagenicity thought to be due to a temperature increase May be due to temperature changes

w32x

w78x

w79x w80x

w81x

w82x

w83x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

Exposure conditions

Mice

Dominant lethality

2.45 GHz, exposure during 120 h over an 8-week period, SAR s 5 Wrkg; mated after the exposure period over the following 8 weeks 2.45 GHz, CW, 0.05–20 Wrkg, 6 h over 2 weeks 2.45 GHz, exposure 16 hrday for up to 30 days; SAR F 20 Wrkg 2.45 GHz, exposure at SAR s F112 Wrkg for up to 5 min 2.45 GHz, exposure 100 minrday throughout gestation at SAR s 2, 8 or 22 Wrkg 2.7.12 GHz, exposure during 20–40 minrday at SAR s11 Wrkg

Conscious mice

Dominant lethality

Mice

Sperm abnormalities

Conscious mice

Sperm abnormalities

Mice

Embryogenesisrteratogenesis

Mice

Embryogenesisrteratogenesis

Rats

Embryogenesisrteratogenesis

6 GHz, SAR s 7 Wrkg, exposure 8 hr day throughout pregnancy

Rats

Embryogenesisrteratogenesis

2.45 GHz, 100 minrday from day 6 to day 15 of gestation at 6 or 4 Wrkg 2.45 GHz, 6 hrday throughout gestation; estim ated SA R s 2 – 4 Wrkg

Rats

Embryogenesisrteratogenesis

Rats

Embryogenesisrteratogenesis

Reduced pregnancy rate and pre-implantation survival. No dominant lethality No effect on pregnancy rates, pre-implantation survival or testes weight.

Increased frequency of sperm abnormalities No significant effect on sperm count and number of abnormal sperm Mainly exencephaly

Significant decreased mean mass of live foetuses in the high exposure group Abnormal development, embryorfoetal deaths at all stages of development

Slight growth retardation no evidence of increased embryo or foetal deaths or of developmental abnormalities subtle behavioural effects were noticed post-natally Significant mean body weight of the foetuses at 6 Wrkg No effect

Effects probably the result of a heating effect

w84x

w85x

w86x Testes temperature unaffected

w87x

Effects increased with increasing exposure

w88x

No abnormal raise in body temperature

w89x

Rectal temperature raised to 438C. Teratogenicity directly related to the temperature of the dam during exposure and to the duration of exposure Here the SAR was reported to be insufficient to raise the body temperature significantly

w90–92x

Maternal temperatures raised to about 408C Žboth exposure conditions. No increased rectal temperature

w95,96x

w93,94x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

2.45 GHz, CW, 43 Wrkg during 30 min

w97,98x

151

152

Exposure conditions

Animal species

Biological endpoint

Main results

Comments

Reference

915 MHz, 6 hrday throughout pregnancy, estim ated S A R s 3.5 Wrkg 100 MHz, 0.4 Wrkg, 6 h 40 minrday on day 6–11 of gestation 27.12 MHz at 1 Wrm2 from day 0 up to day 20 of gestation, SAR s10–4 Wrkg 2.45 GHz, SAR s 7, 28 or 40 Wrkg, 8 hrday for various times of gestation

Rats

Embryogenesisrteratogenesis

No effect

Maternal temperature unaffected

w99,100x

Rats

Embryogenesisrteratogenesis

No effect

Rats

Embryogenesisrteratogenesis

Mice

Embryogenesisrteratogenesis

Mice

Embryogenesisrteratogenesis

Significant decrease in post-implantation survival and reduced cranial ossification Significant reduction in implantation sites per litter and in foetal weight at 40 Wrkg and exposure during day 1–6; significant increase in % of m alform ed foetuses Žmainly cleft palate. for exposures at day 6–15 Žsame SAR.; not confirmed at later experiment Lowered foetal weight and delayed skeletal maturation persistent delay of brain maturation

2.45 GHz, CW, 100 minrday during 6–17 days of gestation, SAR s 16 Wrkg

w101x

Normal rectal temperature results difficult to reconcile with other investigations Colonic temperature rose by 1 or 2.38C in the 2 highest exposure groups; respective exposure levels assumed to be at threshold

w102x

w103,104x

w105,106x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

Table 3 Žcontinued.

Syrian hamster

Embryogenesisrteratogenesis

2.45 GHz, 2 hrday, 7 daysrweek on day 1–7, 8–18 or 1–18 of gestation, SAR s6 or 9 Wrkg

Mice

Embryogenesisrteratogenesis

2.45 GHz et 10, 100 or 400 Wrm2 , SAR s 0.5, 4–5 and 16–18 Wrkg, 2 hrday from day 1 to 18 of gestation

Mice

Embryogenesisrteratogenesis

10 MHz, continuous waves, SAR s6.6 Wrkg 2-methoxyethanol Žoral intake. administration 5 min before RF irradiation 2.45 GHz

Rats

Embryogenesisrteratogenesis

Mice

Sex-linked lethals

recessive

Increased foetal deaths, decreased foetal weight and decreased skeletal maturity observed at the highest SAR-values Significant reduction in post-implantation survival; increased intracranial and intra-abdominal bleeding; post-natally markedly decreased resistance to viral and bacterial infection Enhanced effect of the chemical teratogen cytosine arabinoside Ž10 mgrkg on day 9.; microwaves alone resulted in reduced foetal body mass ŽŽ4–5 Wrkg.; increased post-implantation deaths Ž16–18 Wrkg. Combined exposures enhance the foetal malformation frequency as well as the severity of malformations No difference between sham-exposed and RFexposed animals

Mean maternal rectal temperature raised 0.4 and 1.68C resp.

w107x

Rectal temperature increased by 1.5–2.08C during each exposure

w108x

28C increased rectal temperature in highest exposure group

w109x

w110x

Rectal temperature in the highest exposed group rose by up to 38C

w33x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

2.45 GHz, 100 minrday from day 6–14 of gestation, SA R s 16 – 18 Wrkg

153

154

Exposed subjects Professionally exposed sub jects; frequencies ranging from 400 kHz to 20 GHz

Cells investigated Human lymphocytes

Genetic endpoint Chromosome aberrations

Professionally exposed subjects Ž10 mWrcm2 ., frequencies ranging from 1250 to 1350 MHz

Human lymphocytes

Micronuclei

Main results No increase in chromosome damage found in radio-lineman who work with radiofrequencies at or below occupational exposure limits Increased micronucleus frequency in exposed subjects compared to controls

Comments Exposure to RF-fields is relatively pure Žno known other Žprofessionally. exposures

Reference w44x

Workers exposed to other environm ental influ ences?

w43x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

Table 4 Overview of investigations on RF-induced genetic effects in human subjects

Table 5 A few in vitro cancer related studies Biological model

Biological endpoint

Main results

Comments

Reference

Cells in test-tubes exposed for 3–5 days in anechoic chamber to pulsed 10 cm microwaves from a box horn antenna Amplitude modulated 45 O MHz waves, 10 Wrm2 , eventually after TPA application Amplitude modulated microw aves, SA R s 3 Wrkg Amplitude modulated microwaves, SAR s 0.1– 4.4 Wrkg, eventually combined with X-rays, followed by treatment with TPA

Human lymphocytes

Lymphoblastoıd ¨ transformation

Induction of lymphoblastoıd ¨ transformation by the microwave radiation

According to control experiments the effect was not due to a heating effect

w111x

Reuber H35 hepatoma cells, CHO cells and 294 T human melanoma cells

ODC activity

Increased ODC activity

Mouse fibroblasts

ODC activity

Increased ODC activity

C3H10T1r2 cells

in vitro cell transformation

Enhanced cell transformation

2.45 GHz

Human red blood cells

Naq,Kq-ATPase activity

2.45 GHz, CW, SAR s 5–20 Wrkg

Glioma cells or human lymphocytes

27 MHz or 2.45 GHz, CW, SAR s 5 or 25 Wrkg

CHO cells

RNA precursor w 3 Hxuridine or DNA precursor w 3 Hxthymidine incorporation Cell cycle alterations

Inhibition of Naq,KqATPase activity Elevated transcription and proliferation at SAR s 25 Wrkg but unchanged at higher SARs Cell cycle alterations found at both frequencies, 2.45 GHz being more effective in inducing alterations

w48x

Increase is at much lower level than treatment with a chemical promoter Some inconsistency was found between the different studies. Furthermore, C3H10T1r2 cells are chromosomally abnormal and their response to proliferative stimuli may be atypical

w49,112x

w113–115x

w45x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

Exposure conditions

w46,47x

Exposure under ‘‘isothermal’’ conditions Ž37" 0.28C.

w116x

155

156

Table 6 Review of some cancer studies in RF or microwave exposed laboratory animals Biological model

Biological endpoint

Results

Comments

References

9.27 GHz, 2 ms pulses at 500 pps, 1000 Wrm2 , 4 .5 m in r d a y , 5 daysrweek for 59 weeks 800 MHz, 2 hrday; 5 daysrweek over a period of 25 weeks. SAR up to 1.5 Wrkg

Swiss mice

Post-mortem analysis

Microwave-induced leucosis

The investigation was severely criticised for several reasons

w117x

RFM adult mice

Effect on longevity

5 Hz pulses of 447 kVrm peak electric field strength; 5 daysrweek for 33 weeks

AKRrJ male mice

Leukaemia

2.54 GHz pulsed at 800 Hz; SAR s 015 – 0.4 Wrkg

Sprague-Dawley rats

General health longevity

Non-significant increase in the life-span of the exposed mice compared to the controls. No significant changes in mean red and white blood cells 21% of exposed mice had leukaemia at the end of the exposure compared to 46% in the sham-exposed group Significant raise in overall incidence of malignancies

2.45 GHz, 35 Wrkg; 20 minrday during days 11–14 of gestation

CFW mice exposed in utero. Mice injected with lymphoreticular sarcoma cells at day 16 of age and further irradiated or not

Tumour incidence

and

Significantly lower tumour incidence in mice irradiated in utero and irradiated or sham-irradiated post-natally. Mice irradiated in utero and followed for 36 months had initially a lower tumour development rate, but then the rate increased to become similar

w118x

Absence of complete analysis of leukaemia incidence precludes any definite conclusion

w119x

The biological significance of the results was questioned by the authors because the higher incidence level of specific malignancies was similar to what was previously reported as being normal for untreated rats

w120x

w121x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

Exposure conditions

BALBrc mice s.c. injected prior to irradiation with mouse sarcoma cells

Tumour growth and lung metastases

2.45 GHz, 500 Wrm2 , SAR s 25 Wrkg; 2 hr day for 7 days

Idem but irradiation prior to injection of sarcoma cells

Tumour growth and lung metastases

2.45 GHz, 50 or 150 Wrm2 , SAR up to 3 and 8 Wrkg resp.; 2 hrday, 6 daysrweek

C3HrHe mice Žirradiated at age 6 weeks to 12 months. or BALBrC mice irradiated 1 or 3 months prior to or simultaneously with exposure to benzow axpyrene

Effect of microwaves on tumour growth and lung cancer colony assay

2.45 GHz, CW or PW Ž10 ms pulses for 10 ms repeated at 25 Hz.; SAR s1.2 Wrkg

C57BLr6 J mice, irradiation 15 days exposure prior to s.c. injection of 3=10 6 B16 melanoma cells and during subsequent tumour development Sprague-Dawley rats

Effect of microwaves on tumour progression

Low level pulsed 2.45 GHz waves, SAR up to 0.4 Wrkg; exposure from 2 to 27 months of age

Life time study including determination of cause of death, frequency and site of neoplastic and nonneoplastic lesions

Temporary tumour regression followed by renewed growth 12 days later. More lung metastases in the exposed group compared to controls but mean survival time greater in exposed animals Ž53 days vs. 38 days. Significantly accelerated tumour growth and increase in the number of lung metastases. Mean survival time shortened in irradiated mice SAR-dependent acceleration of both mammary tumours in C3HrHeA mice and skin tumours in BALBrc mice. Microwave exposure resulted in an increase in the number of L1sarcoma cell colonies in the lungs of irradiated mice No effect on the rate of development of melanoma or on the mean survival time Ž25 days.

No clear evidence of an increase in tumour incidence as a result of exposure to microwaves

w122x

w122x

C3HrHeA mice are genetically predisposed to m am m ary tu m o u rs. BABLrc mice exposed to 3,4-benzopyrene by skin painting Ž5 months treatment. 2–3 Wrkg gave results similar to the effect of overcrowding Žchronic stress.

w54x

w52x

Data should eventually be re-analysed

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

2.45 GHz, 500 Wrm2 , SAR s 25 Wrkg; 2 hr day for 7 days

w123,124x

157

158

Table 6 Žcontinued. Biological model

Biological endpoint

Fisher 344 rats, injected with rat glioma cells

Histopathological examination

BALBrc mice, 4 weeks old. Animals injected with dimethylhydrazine ŽDMH. once per week during the course of the microwave treatment. A group DMH-treated animals were also exposed to TPA once per week for 10 weeks from the third week on after initial treatment E m-Pim1 transgenic mice

900 MHz pulsed at 217 Hz and pulse width of 0.6 ms. Two half-hour exposure periods per day for 18 months. SAR s 0.13– 0.4 Wrkg

Results

Comments

References

No significant difference in tumour size between experimental and control animals

w53x

Colon tumour incidence

The 2.45 GHz microwave radiation at 10 mWrm2 did not promote DMH-induced colon cancers in young mice

w51x

Lymphoma

Lymphoma risk was found to be significantly higher in the exposed mice than in the controls

brain

This study does not indicate that RF-field exposure would be specifically lymphomagenic in normal mice. So far the significance of the finding for mobile phone-linked human health is not clear

w55x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

Exposure conditions 915 MHz, CW, 1 W and modulated with 4,8,16 and 200 Hz in 0.5 ms pulses, and 50 Hz in 6 ms pulses Ž2 W per pulse., 7 hrday, 5 daysrweek during 3 weeks 2.45 GHz, 10 mWrcm2 in anechoic chamber, 3 hrday, 6 daysrweek over a 5-month period. SAR s10–12 Wrkg

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

5.2. Teratogenicity Several studies have shown that sufficiently elevated body temperatures are teratogenic to a number of mammalian species, including primates Že.g. w34– 36x.. As microwave Žor RF.-induced teratogenic effects were usually accompanied by a significant rise in maternal body temperature, they hence could be ascribed to this thermal effect Žsee w37x for a review.. Yet, the results of studies on microwave induced foetal loss and developmental malformations were sometimes inconsistent with others. This is most probably due to species differences with regard to their thermo-susceptibility; rats appear more likely to lose heat-damaged embryos than to give birth to malformed young w34x, whereas in other mammals a wider range is observed between a teratogenic exposure and a lethal exposure. Overall, the conclusion should be that the evidence suggests that only exposures that have an appreciable heating effect are likely to affect the embryo adversely. 5.3. Somatic cell genetic effects Most studies that were published so far did not demonstrate convincingly any direct DNA damage after acute or chronic exposure of biological systems to RF-fields Že.g. w17,19x., in particular when temperatures were maintained within normal physiological limits. However, especially two recent investigations have suggested that RF-fields yet can affect DNA Žsee Table 2.. In the first, Sarkar et al. w38x found evidence of an alteration in the length of a DNA microsatellite sequence in cells from brain and testis of mice exposed to 2.45-GHz fields. In another series of experiments, Lai and Singh w39,40x demonstrated that acute exposure to low-intensity radiofrequency radiation increased DNA strand breaks in brain cells of the rat. Furthermore, DNA doublestrand breaks were lower in animals to which the opioid antagonist naltrexone was injected immediately before and after the RF-exposure w41x. These data support the hypothesis that radiofrequency radiation activates endogenous opioids in the brain which in turn cause biological effects w42x. Before speculating about the possible consequences of these find-

159

ings, especially with regard to the use of cellular phones Žwhich was abundantly done in the media., it should be realised that the data were obtained for more than a worst-case exposure situation and for 2450-MHz fields that do not correspond to mobile phone frequencies. The significance of these data, therefore, remain unclear to date. These experiments should also be replicated before the results can be used in any health risk assessment, especially given the weight of evidence suggesting that RF fields are not genotoxic. In humans only few studies have been performed ŽTable 4.. An increased incidence in micronucleated white blood cells from professionally exposed subjects was found in one investigation w43x, but it is not clear to what extent the subjects were also exposed to other environmental influences. A previous cytogenetic investigation of radio-linemen that were almost solely exposed to RF-fields gave negative results w44x. We are presently performing another study on maintenance workers being professionally exposed to microwaves of different frequencies, and so far we have not found a cytogenetic effect in these subjects as compared to non-exposed control subjects. However, the study is not yet completed and in particular some Žin vitro. synergy experiments should be repeated. According to above Žand other. cytogenetic investigations, it must be clear that caution must be exercised in making any general conclusion on the clastogenicity, genotoxicity and heritable effects of radiofrequency fields and microwaves.

6. Cancer-related in vitro investigations As stated above, the evidence for a clastogenic or genetic effect of microwaves is rather contradictory, although overall it may be concluded that RFfieldsrmicrowaves are not genotoxic under non-thermal conditions. Therefore it may also be concluded that RF-fields or microwaves are not tumour initiators and that, if they are somehow related to carcinogenicity, this should be by some other mechanism Že.g. by influencing tumour promotion or by increasing the uptake of carcinogens in cells.. Table 5 summarises most relevant investigations on in vitro cancer related RF-effects. It shows that RF-fields

160

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

may affect ion fluxes through cell membranes Žimportant signalling mechanisms. via effects on ion pumps such as Naq,Kq-ATPase w45x in human red blood cells exposed to RF and microwave radiation. Non-thermal effects were also reported on gross transcription as measured by incorporation of specific RNA or DNA precursor w 3 Hxuridine or w 3 Hxthymidine w46,47x. Cell transformation was shown to be induced in a dose-dependent way Žincrease with increasing SAR value. and according to a series of papers, low-level Hz-modulated microwave radiation may affect intracellular activities of enzymes involved in neoplastic promotion without measurable influence on the overall DNA synthesis. For example, a number of investigations brought some evidence of an effect on intracellular levels of ornithine decarboxylase ŽODC. which is an enzyme usually implicated in tumour promotion w48,49x. Tumour promoters do increase the ODC synthesis. This was also found for microwaves although the microwave effect was much weaker and occurred only for certain modulations of the carrier wave. To date it is not very clear what these results mean in terms of in vivo carcinogenesis.

7. Cancer-related in vivo investigations A relatively large number of in vivo investigations, mainly on 2450-MHz waves but also on other frequencies, have already been performed ŽTable 6 and w50x.. Results of many cancer investigations Žespecially when ongoing and so far unpublished investigations are included. do not support the suggestion that even an extensive daily exposure to EMF causes tumour growth or tumour promotion Že.g. w51–53x.. Overall, the evidence for a cocarcinogenic effect or a RF-induced influence on tumour progression is not substantive. Yet, there were a few positive results that are sufficiently indicative to merit further investigation. This is the case for the investigation of Szmigielski et al. w54x w h o o b se rv e d fa ste r d e v e lo p m e n t o f benzow axpyrene-induced skin tumours in mice that were exposed for some months to sub-thermal 2450MHz microwaves. Also, a very recent investigation on transgenic mice expressing an activated Pim1 oncogene in their lymphoid cells furthermore turned

up to be probably the most significant finding yet of adverse effects w55x. The mice were exposed to pulsed digital ŽGSM-type. phone radiation at a power density roughly equal to a cell-phone transmitting for two half-hour periods each day. A significant increase in B-cell lymphoma was evident early in the experiment, but the incidence continued to rise over the 18-month exposure period. The experiment was conducted in the ‘‘far field’’ at distances greater from the mice than the cell phone is normally held from the head. It is not yet clear what these results mean in terms of public health, but it seems clear that they should be taken seriously and prompt further research.

8. Other cancer-related studies The above-mentioned investigations may be considered more or less directly related to cancer. Other investigations on other physiological processes may of course also be related to cancer. This is especially true for effects on the immune system. It is indeed well known that the immune system plays an important role in controlling the proliferation of cancer cells. Therefore, numerous studies have also been performed at various power levels and frequencies. However, these investigations are well beyond the scope of this report and will therefore not be discussed in detail. The interested reader can find some excellent review papers on this subject Že.g. this issue and w18,56–58x..

9. Conclusion Today, it is still not very clear whether proper use of radiofrequency fields and microwave-emitting devices may be harmful to human beings. Many investigations have been performed in the past and many different end-points have been studied. Investigations on genetic- or cancer-related effects are among them. It was almost invariably found that biological effects of acute exposure to these fields were consistent with responses to induced heating, resulting in frank rises in cellular, tissue or body temperature of 18C or more. This is consistent with a SAR-value above 1–2 Wrkg. Most often, experimental Žthermal. con-

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

ditions are not encountered in normal life situations or correspond to a worst-case situation that may occur for short periods of time. However, in the case of low-level exposures, the site of energy deposition might be such that micro-heating could occur. Some data are rather puzzling, and effects obtained under non-thermal conditions should require further investigations. There is a need for better understanding of this type of interaction. In particular, synergistic effects and mechanistic investigations should be highlighted. With regard to potential health effects of mobile phones, especially long term effects, the available data are at present too scarce. Further studies are needed before any valid conclusion can be drawn.

w13x

w14x

w15x

w16x

w17x

References w1x S.F. Cleary, B.S. Pasternack, G.W. Beebe, Cataract incidence in radar workers, Arch. Environ. Health 11 Ž1965. 179–182. w2x F.C. Hollows, J.B. Douglas, Microwave cataract in radiolinemen and controls, Lancet ii Ž1984. 406–407. w3x L. Martens, J. De Moerloose, D. De Zutter, Calculation of the electromagnetic fields induced in the head of an operator of a cordless telephone, Radio Sci. 30 Ž1995. 283–290. w4x A.W. Guy, The starting point: wireless technology research, L.L.C.’s dosimetry risk evaluation research, Hum. Ecol. Risk Assess. 3 Ž1997. 25–50. w5x U. Bergqvist, Review of epidemiological studies, in: N. Kuster, Q. Balzano, J.C. Lin ŽEds.., Mobile Communication Safety, Chapman and Hall, London, 1997, pp. 147–170. w6x H.I. Bassen, RF interference of medical devices, in: N. Kuster, Q. Balzano, J.C. Lin ŽEds.., Mobile Communication Safety, Chapman and Hall, London, 1997, pp. 65–94. w7x N. Kuster, Q. Balzano, Experimental and numerical dosimetry., in: N. Kuster, Q. Balzano, J.C. Lin ŽEds.., Mobile Communication Safety, Chapman and Hall, London, 1997, pp. 13–64. w8x D.P. Funch, K.J. Rothman, J.E. Luoghlin, N.A. Dreuer, Utility of telephone company records for epidemiologic studies of cellular phones, Epidemiology 7 Ž1996. 299–302. w9x K.J. Rothman, C.-K. Chou, R. Morgan, Q. Balzano, A.W. Guy, D.P. Funch, S. Preston-Martin, J. Mandel, R. Steffens, G. Carlo, Assessment of cellular telephone and other radio frequency exposure for epidemiologic research, Epidemiology 7 Ž1996. 291–298. w10x K.J. Rothman, J.E. Luoghlin, D.P. Funch, N.A. Dreyer, Overall mortality of cellular telephone customers, Epidemiology 7 Ž1996. 303–305. w11x L. Verschaeve, Can nonionising radiation induce cancer?, Cancer J. 8 Ž1995. 237–249. w12x A.M. Lilienfield, J. Tonascia, S. Tonascia, et al., Evaluation

w18x

w19x

w20x

w21x

w22x

w23x

w24x

w25x

w26x

w27x

161

of health status of foreign service and other employees from selected Eastern European posts. Final report to US Department of State. Baltimore: Johns Hopkins School of Public Health, Department of Epidemiology, 1978 Žcited in w5x.. S. Milham, Increased mortality in amateur radio operators due to lymphatic and hematopoietic malignancies, Am. J. Epidemiol. 127 Ž1988. 50–54. B. Armstrong, G. Theriault, P. Guenel, J. Deadman, M. ´ ´ Goldberg, P. Heroux, Association between exposure to ´ pulsed electromagnetic fields and cancer in electric utility workers in Quebec, Canada, and France, Am. J. Epidemiol. 140 Ž1994. 805–820. C.D. Robinette, C. Silverman, S. Jablon, Effect upon health of occupational exposure to microwave radiation Žradar., Am. J. Epidemiol. 112 Ž1980. 39–53. S. Szmigielski, Cancer morbidity in subjects occupationally exposed to high-frequency Žradiofrequency and microwave. electromagnetic radiation. Sci. Total Environ., 180 Ž1997. 9–17. A. Leonard, A.J. Berteaud, A. Bruyere, ´ ` An evaluation of the mutagenic, carcinogenic and teratogenic potential of microwaves, Mutation Res. 123 Ž1983. 31–46. R.D. Saunders, C.I. Kowalczuk, Z.J. Sienkiewicz, Biological Effects of Exposure to Non-ionising Electromagnetic Fields and Radiation: III. Radiofrequency and Microwave Radiation, National Radiological Protection Board, Chilton, UK, NRPB-R240, 1991. WHO, Electromagnetic fields Ž300 Hz to 300 GHz., Environmental Health Criteria 137, WHO, Geneva, 1993, pp. 290. G. d’Ambrosio, M.B. Lioi, M.R. Scarfi, O. Zeni, Genotoxic effects of amplitude-modulated microwaves on human lymphocytes exposed in vitro under controlled conditions, Electro-Magnetobiol. 14 Ž1995. 157–164. M.T. Alam, N. Barthakur, N.C. Lambert, S.S. Kasatiya, Cytological effects of microwave radiation in Chinese hamster cells in vitro, Can. J. Genet. Cytol. 20 Ž1978. 23–30. A. Maes, L. Verschaeve, A. Arroyo, C. De Wagter, L. Vercruyssen, In vitro cytogenetic effects of 2450 MHz waves on human peripheral blood lymphocytes, Bioelectromagnetics 14 Ž1993. 495–501. V. Garaj-Vrhovac, D. Horvat, Z. Koren, The relationship between colony-forming ability, chromosome aberrations and incidence of micronuclei in V79 Chinese hamster cells exposed to microwave radiation, Mutation Res. 263 Ž1991. 143–149. T. Haider, S. Knasmueller, M. Kundi, M. Haider, Clastogenic effects of radiofrequency radiations on chromosomes in Tradescantia, Mutation Res. 324 Ž1994. 65–68. D.J. Brusick, An Assessment of the Genotoxic Activity of Radiofrequency Radiation, State of the Science Colloquium, Rome, 1995. A. Maes, M. Collier, D. Slaets, L. Verschaeve, 954 MHz microwaves enhance the mutagenic properties of mitomycin C, Environ. Mol. Mutagen. 28 Ž1996. 26–30. A. Maes, M. Collier, U. Van Gorp, S. Vandoninck, L. Verschaeve, Cytogenetic effects of 935.2-MHz ŽGSM. mi-

162

w28x

w29x w30x

w31x

w32x

w33x

w34x

w35x w36x

w37x w38x

w39x

w40x

w41x

w42x

w43x

w44x

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165 crowaves alone and in combination with mitomycin C, Mutation Res., 393 Ž1997. 151–156. M. Gillois, C. Auge, C. Chevalet, Effet des ondes electromagnetiques non-ionisants sur la viabilite´ et l’heredite ´ ´ ´´ ´ des cellules de mammiferes in: Sympo` en culture etablie, ´ sium International: Ondes electromagnetiques et Biologie, ´´ ´ 30 juin-4 juillet, Jouy-en-Josas, France, 1980, pp. 9–15. J. Holt, A. Nelson, Four years of microwaves in cancer therapy, J. Belge Radiol. 62 Ž1976. 467–476. S.A. Gunn, T.C. Gould, W.A.D. Anderson, The effect of microwave radiation on morphology and function of rat testis, Lab. Invest. 10 Ž1961. 301–314. C.I. Kowalczuk, R.D. Saunders, H.R. Stapleton, Sperm count and sperm abnormality in mice after exposure to 2.45 GHz microwave radiation, Mutation Res. 122 Ž1983. 155– 161. R.D. Saunders, C.I. Kowalczuk, Effects of 2.45 GHz microwave radiation and heat on mouse spermatogenic epithelium, Int. J. Radiat. Biol. 40 Ž1981. 623–632. C.V. Beechey, D. Brooker, D. Kowalczuk, C.I. Saunders, A.G. Searle, Cytogenetic effects of microwave irradiation on male germ cells of the mouse, Int. J. Radiat. Biol. 50 Ž1986. 909–918. M.J. Edwards, R.A. Wanner, in: J.G. Wilson, F. Clark, ŽEds.., Handbook of Teratology, Vol. 1. General Principles and Ethiology, Plenum, New York, 1977, p. 421. M.J. Edwards, Congenital effects due to hyperthermia, Adv. Vet. Comp. Med. 22 Ž1978. 29–52. D. Poswillo, H. Nunnerly, D. Sopher, J. Keith, Hyperthermia as a teratogenic agent, Ann. R. Soc. Coll. Surgeons 55 Ž1974. 171–174. M.E. O’Connor, Mammalian teratogenesis and radiofrequency fields, Proc. IEEE 68 Ž1980. 56–60. S. Sarkar, S. Ali, J. Behari, Effect of low power microwave on the mouse genome: A direct DNA analysis, Mutation Res. 320 Ž1994. 141–147. H. Lai, N.P. Singh, Acute low-intensity microwave exposure increases DNA single-strand breaks in rat brain cells, Bioelectromagnetics 16 Ž1995. 207–210. H. Lai, N.P. Singh, Single- and double-strand DNA breaks in rat brain cells after acute exposure to radiofrequency electromagnetic radiation, Int. J. Radiat. Biol. 69 Ž1996. 513–521. H. Lai, M. Carino, N. Singh, Naltrexone blocks RFR-induced DNA double strand breaks in rat brain cells, Ž1997. in press. H. Lai, Research on the neurological effects of non-ionizing radiation at the university of Washington, Bioelectromagnetics 13 Ž1992. 513–526. A. Fucic, V. Garaj-Vrhovac, M. Skara, B. Dimitrovic, X-rays, microwaves and vinyl chloride monomer: their clastogenic and aneugenic activity, using the micronucleus assay on human lymphocytes, Mutation Res. 282 Ž1992. 265–271. O.M. Garson, T.L. McRobert, L.J. Campbell, B.A. Hocking, I. Gordon, A chromosomal study of workers with

w45x

w46x

w47x

w48x

w49x

w50x

w51x

w52x

w53x

w54x

w55x

w56x

w57x

long-term exposure to radio-frequency radiation, Med. J. Aust. 155 Ž1991. 289–292. J.W. Allis, B.L. Sinha-Robinson, Temperature-specific inhibition of human cell NaqrKqATPase by 2450 MHz microwave radiation, Bioelectromagnetics 8 Ž1987. 203–207. S.F. Cleary, L.-M. Liu, R.E. Merchant, Glioma proliferation modulated in vitro by isothermal radiofrequency radiation exposure, Radiat. Res. 121 Ž1990. 38–45. S.F. Cleary, L.-M. Liu, R.E. Merchant, In vitro lymphocyte proliferation induced by radio-frequency electromagnetic radiation under isothermal conditions, Bioelectromagnetics 11 Ž1990. 47–56. C.V. Byus, K. Kartun, S. Pieper, W.R. Adey, Increased ornithine decarboxylase activity in cultured cells exposed to low energy modulated microwave fields and phorbol ester tumour promoters, Cancer Res. 48 Ž1988. 4222–4226. L.M. Penafiel, T. Litovitz, D. Krause, A. Desta, J.M. Mullins, Role of modulation on the effect of microwaves on ornithine decarboxylase activity in L929 cells. Bioelectromagnetics, 18 Ž1997. 132–141. S. Szmigielski, M. Bielec, M. Lipski, G. Sokolska, Immunologic and cancer-related aspects of exposure to lowlevel microwave and radiofrequency fields, in: A.A. Marino ŽEd.., Modern Bioelectricity, Marcel Dekker, New York, 1988, 861-869. R.Y. Wu, H. Chiang, B.J. Shao, N.G. Li, Y.D. Fu, Effects of 2.45 GHz microwave radiation and phorbol ester 12-Otetradecanoylphorbol-13-acetate or dimethylhydrazine-induced colon cancer in mice, Bioelectromagnetics 15 Ž1994. 531–538. R. Santini, M. Honsi, P. Deschaux, H. Pacheco, B16 melanoma development in black mice exposed to low-level microwave radiation, Bioelectromagnetics 9 Ž1988. 105– 107. L.G. Salford, A. Brun, B.R.R. Persson, J. Eberhardt, Experimental studies of brain tumour development during exposure to continuous and pulsed 915 MHz radiofrequency radiation, Bioelectrochem. Bioenerget. 30 Ž1993. 313–318. S. Szmigielski, A. Szudzinski, A. Pietraszek, M. Bielec, J.K. Wrembel, Accelerated development of spontaneous and benzopyrene-induced skin cancer in mice exposed to 2450 MHz microwave radiation, Bioelectromagnetics 3 Ž1982. 179–191. M.H. Repacholi, A. Basten, V. Gebski, D. Noonan, J. Finnie, A.W. Harris, Lymphomas in E m-Pim1 transgenic mice exposed to pulsed 900 MHz electromagnetic fields, Radiation Res. 147 Ž1997. 631–640. G.L. Carlo, I. Munro, A.W. Guy, Potential public health risks from wireless technology, in: Research Agenda for the Development of Data for Science-based Decisionmaking, Scientific Advisory Group on Cellular Telephone Research, Washington, DC, 1994, pp. 87–95. P. Polson, L.N. Heynick, Overview of the radiofrequency radiation bioeffects database, in: B.J. Kleuenberg, M. Grandolfo, D. Erwin ŽEds.., Radiofrequency Radiation Standards. Biological Effects, Dosimetry, Epidemiology and

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

w58x

w59x

w60x

w61x

w62x

w63x

w64x

w65x

w66x

w67x

w68x

w69x

w70x

w71x

w72x

Public Health Policy, NATO ASI Series A; 274, 1994, 337-388. R.J. Smialowicz, Immunological effects of nonionizing electromagnetic radiation, IEEE Eng. Med. Biol. Mag. 6 Ž1987. 47–51. P.E. Hamrick, Thermal denaturation of DNA exposed to 2450 MHz CW microwave radiation, Radiat. Res. 56 Ž1973. 400–404. K.T.S. Yao, Cytogenetic consequences of microwave incubation of mammalian cells in culture, Genetics 83 Ž1976. s84. K.T.S. Yao, Cytogenetic consequences of microwave irradiation on mammalian cells incubated in vitro, J. Hered. 73 Ž1982. 133. D.C. Lloyd, R.D. Saunders, P. Finnon, C.I. Kowalczuk, No clastogenic effect from in vitro microwave irradiation of G0 lymphocytes, Int. J. Radiat. Biol. 46 Ž1984. 135–141. D.C. Lloyd, R.D. Saunders, J.E. Moquet, C.I. Kowalczuk, Absence of chromosomal damage in human lymphocytes exposed to microwave radiation with hyperthermia, Bioelectromagnetics 7 Ž1986. 235–237. V. Garaj-Vrhovac, D. Horvat, Z. Koren, The effect of microwave radiation on the cell genome, Mutation Res. 243 Ž1990. 87–93. V. Garaj-Vrhovac, A. Fucic, D. Horvat, The correlation between the frequency of micronuclei and specific chromosome aberrations in human lymphocytes exposed to microwave radiation in vitro, Mutation Res. 281 Ž1992. 181– 186. A. Maes, M. Collier, D. Slaets, L. Verschaeve, Cytogenetic effects of microwaves from mobile communication frequencies Ž954 MHz., Electro-Magnetobiol. 14 Ž1995. 91–98. P. Eberle, M. Erdtmann-Vourliotis, S. Diener, H.-G. Finke, B. Loffelholz, A. Schnor, M. Schrader, Zellproliferation, ¨ Schwesterchromatidaustausche, Chromosomenaberrationen, Mikrokerne und Mutationsrate, Newsletter Edition Wissenschaft 4 Ž1996. 5–15. V. Garaj-Vrhovac, S. Vojvodic, A. Fucic, D. Kubelka, Effects of 415 MHz frequency on human lymphocyte genome, in: Proceedings IRPA9 Congress, Vienna, Austria, Vol. 3, 1996, pp. 604–606. V. Ciaravino, M.L. Meltz, D.N. Erwin, Effects of radiofrequency radiation and simultaneous exposure with mitomycin C on the frequency of sister chromatid exchanges in Chinese hamster ovary cells, Environ. Mutagen. 9 Ž1987. 393–399. M.L. Meltz, K.A. Walker, Radiofrequency Žmicrowave. radiation exposure on mammalian cells during UV-induced DNA repair synthesis, Radiation Res. 110 Ž1987. 255–266. M.L. Meltz, P. Eagan, D.N. Erwin, Absence of mutagenic interaction between microwaves and mitomycin C in mammalian cells, Environ. Mol. Mutagen. 13 Ž1989. 294–303. V. Ciaravino, M.L. Meltz, D.N. Erwin, Absence of synergistic effect between moderate-power radio-frequency electromagnetic radiation and adriamycin on cell-cycle progression and sister chromatid exchange, Bioelectromagnetics 12 Ž1991. 289–298.

163

w73x J.J. Kerbacher, M.L. Meltz, D.N. Erwin, Influence of radiofrequency radiation on chromosome aberrations in CHO cells and its interaction with DNA damaging agents, Radiat. Res. 123 Ž1990. 311–319. w74x M.L. Meltz, P. Eagan, D.N. Erwin, Proflavin and microwave radiation: absence of a mutagenic interaction, Bioelectromagnetics 11 Ž1990. 149–157. w75x A.T. Huang, M.E. Engle, J.A. Elder, J.B. Kinn, T.R. Ward, The effect of microwave radiation Ž2450 MHz. on the morphology and chromosomes of lymphocytes, Radio Sci. 12 ŽS. Ž1977. 173. w76x E. Manikowska, J.M. Luciani, B. Servantie, P. Czerski, J. Obrenovitch, A. Stahl, Effects of 9.4 GHz microwave exposure on meiosis, Experientia 35 Ž1979. 388–390. w77x D.I. McRee, G. MacNichols, G.K. Livingston, Incidence of sister chromatid exchange in bone marrow cells of the mouse following microwave exposure, Radiat. Res. 85 Ž1981. 340–348. w78x R.M. Lebovitz, L. Johnson, Testicular function of rats following exposure to microwave radiation, Bioelectromagnetics 4 Ž1986. 107–112. w79x R.M. Lebovitz, L. Johnson, Acute, whole body microwave exposure and testicular function of rats, Bioelectromagnetics 8 Ž1987. 37–46. w80x E. Berman, H.B. Carter, D. House, Tests for mutagenesis and reproduction in male rats exposed to 2.45 GHz ŽCW. microwaves, Bioelectromagnetics 1 Ž1980. 65–76. w81x M.M. Varma, E.L. Dage, S.R. Joshi, Mutagenicity induced by non-ionizing radiation in swiss male mice, in: C.C. Johnson, M. Shore ŽEds.., Biological Effects of Electromagnetic Waves, Vol. 1, Food and Drug Administration, US, ŽFDA., Washington, DC, USNCrURSI Annual Meeting – selected papers, Oct. 20–23, Boulder, CO, 1976, pp. 397– 405. w82x S.N. Goud, M.V. Usha Rani, P.P. Reddy, O.S. Reddy, M.S. Rao, V.K. Saxena, Genetic effects of microwave radiation in mice, Mutation Res. 103 Ž1982. 39–42. w83x M.M. Varma, E.A. Traboulay, Evaluation of dominant lethal test and DNA studies in measuring mutagenicity caused by non-ionizing radiation, in: C.C. Johnson, M. Shore ŽEds.., Biological Effects of Electromagnetic Waves, Vol. 1, Food and Drug Administration, US, ŽFDA., Washington, DC, USNCrURSI Annual Meeting – selected papers, Oct. 20– 23, Boulder, CO, 1976, pp. 386–396. w84x R.D. Saunders, S.C. Darby, C.I. Kowalczuk, Dominant lethal studies in male mice after exposure to 2.45 GHz microwave radiation, Mutation Res. 117 Ž1983. 345–356. w85x R.D. Saunders, C.I. Kowalczuk, C.V. Beechey, R. Dunford, Studies of the induction of dominant lethals and translocations in male mice after chronic exposure to microwave radiation, Int. J. Radiat. Biol. 53 Ž1988. 983–992. w86x E. Manikowska-Czerska, P. Czerski, W.M. Leach, Effects of 2.45 GHz microwaves on meiotic chromosomes of male CBArCAY mice, J. Hered. 76 Ž1985. 71. w87x A.B. Cairnie, R.K. Harding, Cytological studies in mouse testis irradiated with 2.45 GHz continuous-wave microwaves, Radiat. Res. 87 Ž1981. 100–108.

164

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

w88x R. Rugh, E.I. Ginns, H.S. Ho, W.H. Leach, Are microwaves teratogenic?, in: P. Czerski, K. Ostrowski, M.L. Shore, C.H. Silverman, M.J. Suess, B. Waldeskog ŽEds.., Biological Effects and Health Hazards of Microwave Radiation, Polish Medical Publishers, Warsaw, 1974, p. 98. w89x E. Berman, J.B. Kinn, H.B. Carter, Observations of mouse foetuses after irradiation with 2.45 GHz microwaves, Health Phys. 35 Ž1978. 791–801. w90x J.M. Lary, D.L. Conover, E.D. Foley, P.L. Hanser, Teratogenic effects of 27.12 MHz radiofrequency radiation in rats, Teratology 26 Ž1982. 299–309. w91x J.M. Lary, D.L. Conover, P.H. Johnson, J.R. Burg, Teratogenicity of 27.12 MHz radiation in rats is related to duration of hyperthermia exposure, Bioelectromagnetics 4 Ž1983. 249–253. w92x J.M. Lary, D.L. Conover, P.H. Johnson, R.W. Hornung, Dose–response relationship between body temperature and birth defects in radiofrequency-irradiated rats, Bioelectromagnetics 7 Ž1986. 141–149. w93x R.P. Jensh, Studies of the teratogenic potential of exposure of rats to 6000-MHz microwave radiation I. Morphologic analysis at term, Radiat. Res. 97 Ž1984. 272–281. w94x R.P. Jensh, Studies of the teratogenic potential of exposure of rats to 6000-MHz microwave radiation II. Postnatal psychophysiologic evaluations, Radiat. Res. 97 Ž1984. 282– 301. w95x E. Berman, H.B. Carter, D. House, Observations of rat foetuses after irradiation with 2450-MHz ŽCW. microwaves, J. Microwave Power 16 Ž1981. 9–15. w96x E. Berman, H.B. Carter, Decreased body weight in foetal rats after irradiation with 2450-MHz ŽCW. microwaves, Health Phys. 46 Ž1984. 537–542. w97x R.P. Jensh, W.H. Vogel, R.L. Brent, An evaluation of the teratogenic potential of protracted exposure of pregnant rats to 2450-MHz microwave radiation. I. Morphologic analysis at term, J. Toxicol. Environ. Health 11 Ž1983. 23–36. w98x R.P. Jensh, W.H. Vogel, R.L. Brent, An evaluation of the teratogenic potential of protracted exposure of pregnant rats to 2450-MHz microwave radiation II. Postnatal physiologic analysis, J. Toxicol. Environ. Health 11 Ž1983. 37–45. w99x R.P. Jensh, W.H. Vogel, R.L. Brent, Postnatal functional analysis of prenatal exposure of rats to 915 MHz microwave radiation, J. Am. Coll. Toxicol. 1 Ž1982. 73–84. w100x R.P. Jensh, I. Weinberg, R.L. Brent, Teratologic studies of prenatal exposure of rats to 915-MHz microwave radiation, Radiat. Res. 92 Ž1982. 160–171. w101x J.M. Lary, D.L. Conover, P.H. Johnson, Absence of embryotoxic effects from low-level Žnon-thermal. exposure of rats to 100 MHz radiofrequency radiation, Scan. J. Work Environ. health 9 Ž1983. 120–129. w102x S. Tofani, G. Agnesod, P. Ossola, S. Ferrini, R. Bussi, Effects of continuous low-level exposure to radiofrequency radiation on intrauterine development in rats, Health Phys. 51 Ž1986. 489–499. w103x P.S. Nawrot, D.I. McRee, R.E. Staples, Effects of 2.45 GHz

w104x

w105x

w106x

w107x

w108x

w109x

w110x

w111x

w112x

w113x

w114x

w115x

w116x

w117x

w118x

microwave radiation on embryofetal development in mice, Teratology 24 Ž1981. 303–314. P.S. Nawrot, D.I. McRee, M.J. Galvin, Teratogenic, biochemical, and histological studies with mice prenatally exposed to 2.45-GHz microwave radiation, Radiat. Res. 102 Ž1985. 35–45. E. Berman, H.B. Carter, D. House, Reduced weight in mice of offspring after in utero exposure to 2450-MHz ŽCW. microwaves, Bioelectromagnetics 3 Ž1982. 285–291. E. Berman, H.B. Carter, D. House, Growth and development of mice offspring after irradiation in utero with 2450MHz microwaves, Teratology 30 Ž1984. 393–402. E. Berman, H.B. Carter, D. House, Observations of Syrian hamster foetuses after exposure to 2450-MHz microwaves, J. Microwave Power 17 Ž1982. 107–112. B. Chazan, M. Janiak, M. Kobus, J. Marcickiewitcz, M. Troszynski, S. Szmigielski, Effects of microwave exposure in utero on embryonal, foetal and postnatal development of mice, Biol. Neonate 44 Ž1983. 339–347. J. Marcickiewitcs, B. Chazan, T. Niemiek, G. Sokolska, M. Troszynski, M. Luczak, S. Szmigielski, Microwave radiation enhances teratogenic effect of cytosine arabinoside in mice, Biol. Neonate 50 Ž1986. 75–83. B.K. Nelson, D.L. Conover, W.S. Brightwell, P.B. Shaw, D. Werren, R.M. Edwards, J.M. Lary, Marked increase in the teratogenicity of the combined administration of the industrial solvent 2-methoxyethanol and radiofrequency radiation in rats, Teratology 43 Ž1991. 621–634. W. Stodolnik-Baranska, Microwave-induced lymphoblastoid transformation of human lymphocytes in vitro, Nature 214 Ž1967. 102–103. D. Krause, J.A. Brent, J.M. Mullins, L.M. Penafield, R.M. Nardone, Enhancement of ornithine decarboxylase activity in L929 cells by amplitude modulated microwaves, in: Abstracts, 12th Annual Meeting of the Bioelectromagnetics Society, San Antonio, Texas, 1990, 94. E.K. Balcer-Kubiczek, G.H. Harrison, Evidence for microwave carcinogenicity in vitro, Carcinogenesis 6 Ž1985. 859–864. E.K. Balcer-Kubiczek, G.H. Harrison, Induction of neoplastic transformation in C3Hr10T1r2 cells by 2.45 GHz microwaves and phorbol ester, Radiat. Res. 117 Ž1989. 531–537. E.K. Balcer-Kubiczek, G.H. Harrison, Neoplastic transformation of C3Hr10T1r2 cells following exposure to 120 Hz modulated 2.45 GHz microwaves and phorbol ester tumour promoter, Radiat. Res. 126 Ž1991. 65–72. S.F. Cleary, G. Cao, L.M. Liu, Effects of isothermal 2.45 GHz microwave radiation on the mammalian cell cycle: comparison with effects of isothermal 27 MHz radiofrequency radiation exposure, Bioelectrochem. Bioenerget. 39 Ž1996. 167–173. S. Prausnitz, C. Susskind, Effects of chronic microwave irradiation on mice, IRE Trans. Biomed. Electron. 9 Ž1962. 104–108. J.F. Spalding, R.W. Freyman, L.M. Holland, Effects of 800

L. VerschaeÕe, A. Maes r Mutation Research 410 (1998) 141–165

w119x

w120x

w121x

w122x

MHz electromagnetic radiation on body weight, activity, hematopoiesis and life span in mice, Health Phys. 20 Ž1971. 421–424. W.D. Skidmore, S.J. Baum, Biological effects in rodents exposed to 108 pulses of electromagnetic radiation, Health Phys. 26 Ž1974. 391–398. C.-K. Chou, A.W. Guy, L.L. Kunz, R.B. Johnson, J.J. Crowley, J.H. Krupp, Long-term, low-level microwave irradiation of rats, Bioelectromagnetics 13 Ž1992. 469–496. S.H. Preskorn, W.D. Edwards, D.R. Justesen, Retarded tumour growth and greater longevity in mice after foetal irradiation by 2450 MHz microwaves, J. Surg. Oncol. 10 Ž1978. 483–492. W. Roszkowski, J.K. Wrembel, K. Roszkowski, M. Janiak, S. Szmigielski, Does whole-body hyperthermia therapy involve participation of the immune system?, Int. J. Cancer 25 Ž1980. 289–292.

165

w123x A.W. Guy, C.-K. Chou, L.L. Kunz, J. Crowley, J. Krupp, Effects of Long-term Low-level Radiofrequency Radiation Exposure on Rats, Vol. 9, Summary, Brooks Air Force Base, USAF School of Aerospace Medicine, Texas, ASAFSAM-TR-85-11, 1985. w124x L.L. Kunz, R.B. Johnson, D. Thompson, J. Crowley, C.-K. Chou, A.W. Guy, Effects of Long-term Low-level Radiofrequency Radiation Exposure on Rats, Vol. 8, Evaluation of Longevity, Cause of Death, and Histopathological Findings, Brooks Air Force Base, USAF School of Aerospace Medicine, Texas, ASAFSAM-TR-85-11, 1985. w125x D.Z. Vijayalaxmi, M.R. Frei, S.J. Dusch, V. Guel, M.L. Meltz, J.R. Jauchem, Frequency of micronuclei in the peripheral blood and bone marrow of cancer-prone mice chronically exposed to 2450 MHz radiofrequency radiation, Radiat. Res. 147 Ž1997. 495–500.